Per- and polyfluoroalkyl substances (or PFAS) have been used in many consumer products for decades. These toxic molecules persist for a very long time in the environment. They can then enter and accumulate in the body. Studies have already established a link between these substances and several health problems, including certain cancers. Researchers at the Keck School of Medicine set out to further examine the influence of PFAS, particularly those found in drinking water, on cancer risks.
During the manufacturing and use of these products, PFAS are dispersed and permanently pollute the environment. These “perennial pollutants” can also enter the body through ingestion or inhalation. Food and drinking water are the primary routes of human exposure to PFAS. A recent study revealed the detection of one or more types of PFAS in at least 45% of drinking water supplies in the United States, near urban areas.
Substances that induce epigenetic and metabolic changes
Associations have been found between PFAS and various health problems, including certain types of cancer (breast, kidney, testicular). The International Agency for Research on Cancer (IARC) has also classified PFOA (perfluorooctanoic acid) and PFOS (perfluorooctanesulfonic acid) as “carcinogenic” and “potentially carcinogenic” for humans.
There will be an estimated 1.9 million new cases of cancer in the United States in 2023. Endocrine disruptors, such as PFAS, are among the environmental risk factors. They cause alterations in male and female reproduction, epigenetic changes, modifications of neuroendocrinology and metabolism which can lead to the development of cancers.
“ There is therefore strong biological plausibility to link PFAS to cancers », summarize the researchers in the Journal of Exposure Science & Environmental Epidemiology.
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Existing epidemiological studies are limited to associations between PFAS and certain common cancer types. Few studies have examined the effect of PFAS based on their source. In addition, most of them concern European countries. This team of researchers therefore carried out a more in-depth assessment of the cancer risks linked to PFAS in the United States.
Their goal was to look for associations between PFAS in drinking water and cancer incidence at the county level. They hypothesized that some cancers linked to drinking water PFAS have previously gone unnoticed due to the limited sample size of cases and lack of data on these pollutants.
Their study is based on two large data sets. One covers all reported cases of cancer. The other includes all data on PFAS in drinking water across the country. The team used data from 1,080 counties, encompassing a population of approximately 156.1 million people. That’s about half the U.S. population.
Increased incidence for four types of cancer
Data on cancer cases between 2016 and 2021 comes from the National Cancer Institute's Surveillance, Epidemiology, and End Results program. Data on PFAS levels in public drinking water comes from the Environmental Protection Agency's (EPA) Unregulated Contaminant Monitoring Rule programs. They come from two databases: UCMR3 (exposure period: 2013-2015) and UCMR5 (exposure period: 2023-2024).
The researchers took into account several factors that could influence cancer risk. At the individual level, these were age and gender. At the county level, they excluded changes in cancer incidence due to socioeconomic status, smoking rates, obesity prevalence, degree of urbanization, and the presence of other pollutants.
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They then compared each county's cancer incidence and PFAS contamination of drinking water. They took into account the thresholds recommended by the EPA for each of these substances.
Associations between county-level average annual age-adjusted cancer incidence rate (per 100,000 people per year) between 2016 and 2021 and detection or exceedance of the maximum level of PFAS in drinking water, based on UCMR3. Credits: Li et al., Journal of Exposure Science & Environmental Epidemiology (2025)
The team observed a positive association between four types of cancers and the detection of at least one PFAS in water or exceeding the maximum level of contaminants. These cancers affect the digestive system, endocrine system, oral cavity/pharynx and respiratory system.
Effects that differ depending on sex
The strongest association was for detection of PFBS (perfluorobutanesulfonic acid) and oral cavity/pharyngeal cancers. Their incidence is 33% higher in certain communities! Followed by PFNA (perfluorononanoic acid) and PFHpA (perfluoroheptanoic acid), which seem to lead to an increased incidence of cancers of the endocrine system (mainly thyroid).
Based on the most recent data from the EPA, the team estimated that PFAS in drinking water contributes to more than 6,800 incident cancer cases each year!
Illustration of the distribution of PFAS in drinking water and the average annual cancer incidence between 2016 and 2021. Credits: Li et al., Journal of Exposure Science & Environmental Epidemiology (2025)
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The data also show that the incidence of cancer differs depending on sex. In men, four types of cancers were positively associated with the presence of PFAS in water. These are cancers of the urinary system, brain, blood (leukemia) and soft tissues.
In women, PFAS were linked to increased incidence of endocrine, oral cavity/pharyngeal, and soft tissue cancers.
Substances to monitor more closely
This study is the first to examine the links between cancer and PFAS in drinking water in the United States. It proves that exposure to PFAS through drinking water increases the risk of cancer, including rare cancers.
“ The significant associations identified between PFAS and various cancers, including endocrine, digestive, oral cavity, pharyngeal, and respiratory cancers, highlight the urgent need for further research. », conclude the researchers. Individual studies are now needed to determine whether the link is causal. The biological mechanisms at play also remain to be examined.
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In the meantime, these findings add to growing evidence calling for limiting PFAS levels. According to researchers, the proposed regulatory changes may not be enough. “ Some PFAS that have been less studied need more oversight, and regulators need to think about other PFAS that may not yet be heavily regulated said Shiwen Li, first author of the study.
Starting in 2029, the EPA will monitor the levels of six types of PFAS in drinking water. However, stricter limits may be necessary to protect the population.
In France, monitoring of PFAS in drinking water is based on European directive 2020/2184 of December 16, 2020 relating to the quality of water intended for human consumption (EDCH). It imposes a quality limit of 0.10 µg/L for the sum of 20 PFAS in EDCH. Another parameter, “PFAS (total)”, aims to integrate all measurable PFAS in water: its limit is 0.50 µg/L. From January 1, 2026, the health control of EDCH will include systematic research for PFAS.
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